Beta-adrenoreceptor density in cardiac tissue is reduced in many animal models of hypertension. Similarly, physiologic responses of cardiac beta-receptors are impaired in both animals and humans with hypertension. Alterations in beta-receptor-agonist interactions in hypertension have been demonstrated recently in human lymphocytes. Taken together, these studies suggest a fundamental impairment in beta-adrenergic receptor function in hypertension. Because hypertension is primarily a disorder of vascular resistance, it is essential to study the responses of blood vessels in order to examine the functional role of beta-receptor impairment in the pathophysiology of hypertension. Therefore, this study is designed to test the hypothesis that beta receptor-mediated vasodilatation is impaired in borderline hypertension (BHT). There are several novel features of this proposal. (1) I will study vascular, not cardiac, beta-receptors in BHT. I will use venous occlusion plethysmography to study forearm vasodilator responses to isoproterenol (a beta-receptor agonist) in normotensive and borderline hypertensive young adults. (2) Intra-arterial nitroprusside will be used as an internal dilator control to determine if reduced vasodilatation in BHT represents a specific beta-receptor defect. (3) These drugs will be administered intra-arterially to avoid the complicating effects of baroreflexes on vascular tone. (4) Radioligand binding studies of lymphocyte beta-receptor-agonist interactions in vitro will be compared with plethysmographic studies of vascular beta-receptor function in vivo. (5) I will study the functional role of prejunctional beta-receptors in facilitating adrenergic neurotransmission in conscious humans and determine if this prejunctional effect is altered in BHT. Brachial artery infusion of isoproterenol will be used to examine the effects of prejunctional beta-receptor stimulation on 1) reflex neurogenic vasoconstriction, and on (2) net neurotransmitter release as measured by venous-arterial differences in plasma catecholamine concentrations (radioenzymatic assay). These experiments should provide important and new information regarding beta-adrenergic receptor alterations in humans with borderline hypertension. This information should help to explain the pathophysiology of hypertension in young adults. Because hypertension is the most important risk factor for cardiovascular morbidity and mortality, the questions posed have important clinical implications.